Takahashi Kojiro, Toyohira Yumiko, Ueno Susumu, Tsutsui Masato, Yanagihara Nobuyuki
Department of Hospital Pharmacy, University of Occupational and Environmental Health, Kitakyushu, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Nov;374(2):107-16. doi: 10.1007/s00210-006-0098-6. Epub 2006 Oct 7.
We report here the effects of capsaicin, a flavoring ingredient in the hot pepper Capsicum family, on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Capsaicin inhibited catecholamine secretion (IC(50)=9.5, 11.8, and 62 microM) stimulated by carbachol, an agonist of the nicotinic acetylcholine receptor, by veratridine, an activator of voltage-dependent Na(+) channels, and by high K(+), an activator of voltage-dependent Ca(2+) channels, respectively. Capsaicin also suppressed carbachol-induced (22)Na(+) influx (IC(50)=5.0 microM) and (45)Ca(2+) influx (IC(50)=24.4 muM), veratridine-induced (22)Na(+) influx (IC(50)=2.4 microM) and (45)Ca(2+) influx (IC(50)=1.1 microM), and high K(+)-induced (45)Ca(2+) influx (IC(50)=5.8 microM). The reduction in catecholamine secretion caused by capsaicin was not overcome by increasing the concentration of carbachol. Furthermore, capsazepine (10 microM), a competitive antagonist for the transient receptor potential vanilloid 1, and ruthenium red (30 microM), a nonselective cation channel antagonist, did not block the inhibition by capsaicin of catecholamine secretion. Capsaicin also suppressed both basal and carbachol-stimulated (14)C-catecholamine synthesis (IC(50)=10.6 and 26.4 microM, respectively) from [(14)C] tyrosine but not from L: -3, 4-dihydroxyphenyl [3-(14)C] alanine ([(14)C] DOPA) as well as tyrosine hydroxylase activity (IC(50)=8.4 and 39.0 microM, respectively). The present findings suggest that capsaicin inhibits catecholamine secretion and synthesis via suppression of Na(+) and Ca(2+) influx through a vanilloid receptor-independent pathway.
我们在此报告辣椒素（辣椒属植物中的一种调味成分）对培养的牛肾上腺髓质细胞中儿茶酚胺分泌和合成的影响。辣椒素分别抑制了由烟碱型乙酰胆碱受体激动剂卡巴胆碱、电压依赖性钠通道激活剂藜芦定以及电压依赖性钙通道激活剂高钾所刺激的儿茶酚胺分泌（IC(50)分别为9.5、11.8和62微摩尔）。辣椒素还抑制了卡巴胆碱诱导的(22)Na(+)内流（IC(50)=5.0微摩尔）和(45)Ca(2+)内流（IC(50)=24.4微摩尔）、藜芦定诱导的(22)Na(+)内流（IC(50)=2.4微摩尔）和(45)Ca(2+)内流（IC(50)=1.1微摩尔）以及高钾诱导的(45)Ca(2+)内流（IC(50)=5.8微摩尔）。辣椒素导致的儿茶酚胺分泌减少不能通过增加卡巴胆碱的浓度来克服。此外，辣椒素受体1的竞争性拮抗剂辣椒平（10微摩尔）和非选择性阳离子通道拮抗剂钌红（30微摩尔）均不能阻断辣椒素对儿茶酚胺分泌的抑制作用。辣椒素还抑制了基础状态以及卡巴胆碱刺激下由[(14)C]酪氨酸生成(14)C-儿茶酚胺的合成（IC(50)分别为10.6和26.4微摩尔），但不抑制由L-3,4-二羟基苯[3-(14)C]丙氨酸（[(14)C]多巴）生成(14)C-儿茶酚胺的合成，以及酪氨酸羟化酶活性（IC(50)分别为8.4和39.0微摩尔）。目前的研究结果表明，辣椒素通过抑制钠和钙的内流，经由一条不依赖香草酸受体的途径来抑制儿茶酚胺的分泌和合成。
